The overall objective of this project is to understand the molecular mechanism underlying the electrical gating of membrane channels. The concept of aggregation gating is based on the assumption that the ionic pathways responsible for the permeability changes underlying the nerve impulse are formed by a number of subunit proteins. An aggregation channel opens when these subunits assemble in a configuration that creates a pore in the membrane and closes when the pore-forming aggregate changes into a non-conducting configuration. We developed probabilistic methods that allow us to simulate individual kinetic sample paths (Monte Carlo algorithm) and to calculate analytically the expected macroscopic kinetic behavior (Markov process algorithm) from the parameters of the probabilistic formulation of a single gating site. The model can account for the basic microscopic and macroscopic steady-state and kinetic features of biological and model membranes. Experimental protocols for distinguishing the postulated concept from other models and testing its self-consistency were devised. Experiments based on such protocols are carried out on excitable cell membranes in a collaborative effort. The data is evaluated in the context of the proposed concept and other models.